Circular RNAs (circRNAs) are cardinal players in numerous physiological and pathological processes. CircRNAs play dual roles as tumor suppressors and oncogenes in different oncological contexts, including hepatocellular carcinoma (HCC). Their roles significantly impact the disease at all stages, including initiation, development, progression, invasion, and metastasis, in addition to the response to treatment. In this review, we discuss the biogenesis and regulatory functional roles of circRNAs, as well as circRNA–protein–mRNA ternary complex formation, elucidating the intricate pathways tuned by circRNAs to modulate gene expression and cellular processes through a comprehensive literature search, in silico search, and bioinformatics analysis. With a particular focus on the interplay between circRNAs, epigenetics, and HCC pathology, the article sets the stage for further exploration of circRNAs as novel investigational theranostic agents in the dynamic realm of HCC.

The brain requires over one-fifth of the total body oxygen demand for normal functioning. At high altitude (HA), the lower atmospheric oxygen pressure inevitably challenges the brain, affecting voluntary spatial attention, cognitive processing, and attention speed after short-term, long-term, or lifespan exposure. Molecular responses to HA are controlled mainly by hypoxia-inducible factors. This review aims to summarize the cellular, metabolic, and functional alterations in the brain at HA with a focus on the role of hypoxia-inducible factors in controlling the hypoxic ventilatory response, neuronal survival, metabolism, neurogenesis, synaptogenesis, and plasticity.

Erythropoietin (EPO) improves neuronal mitochondrial function and cognition in adults after brain injury and in those afflicted by psychiatric disorders. However, the influence of EPO on mitochondria and cognition during development remains unexplored. We previously observed that EPO stimulates hippocampal-specific neuronal maturation and synaptogenesis early in postnatal development in mice. Here we show that EPO promotes mitochondrial respiration in developing postnatal hippocampus by increasing mitochondrial content and enhancing cellular respiratory potential. Ultrastructurally, mitochondria profiles and total vesicle content were greater in presynaptic axon terminals, suggesting that EPO enhances oxidative metabolism and synaptic transmission capabilities. Behavioural tests of hippocampus-dependent memory at early adulthood, showed that EPO improves spatial and short-term memory. Collectively, we identify a role for EPO in the murine postnatal hippocampus by promoting mitochondrial function throughout early postnatal development, which corresponds to enhanced cognition by early adulthood.

Thiersch, Markus, and Erik R. Swenson. High altitude and cancer mortality. High Alt Med Biol 00:000–000, 2017.—Humans living at high altitude (HA) are exposed to chronic (hypobaric) hypoxia. Despite the permanent stress of hypoxic exposure, humans populating HA areas have reduced cancer mortality over a broad spectrum of cancer types. In fact, the majority of the physiological adaptive processes at HA occurring in response to hypoxia might be the driving force for reduced cancer mortality at HA. In this review, we summarize epidemiological and animal studies that compare cancer incidence and cancer mortality between HA and low altitude or between hypoxia and normoxia, respectively. We discuss the potential role of oxygen-independent and oxygen-dependent mechanisms that might contribute to reduced cancer mortality at HA. Reactive oxygen species and their detoxification as well as the hypoxia-inducible factors are especially promising targets and may be related to why cancer mortality is reduced at HA. In addition, we briefly discuss two aspects with a proven impact on tumorigenesis, namely the immune system and tumor surveillance as well as HA-induced metabolic changes. Further animal and clinical studies are clearly needed to explain why cancer mortality is reduced at HA and to decide whether HA or hypoxia-based therapeutic approaches could be implemented for cancer treatment. However, exposure to HA activates multiple adaptive mechanisms (oxygen independent and oxygen dependent) sharing common pathways as well as activating counteracting pathways, which complicate the identification of specific HA-induced mechanisms of tumor suppression.